Methods for Purifying Polysaccharides and Pharmaceutical Compositions and Medical Devices Containing the Same

Abstract

Methods for removing endotoxin from naturally occurring materials, such as polysaccharides (e.g., agarose and / or carrageenan) are described herein. Polysaccharides that are substantially free of endotoxins and uses thereof are also described. The polysaccharide materials can be isolated from microorganisms, multicellular organisms, such as, algae, plants, seaweed, etc. The method involves the use of acidic and basic solutions to hydrolyze the lipid-polysaccharide bond in endotoxins. Cleaving the fatty acid from the polysaccharide reduces the water-solubility of the fatty acid and enables its removal with an organic solvent such as ethanol. The polysaccharide component can also undergo acidic or basic hydrolysis due to the weak glycosidic bond between the sugar rings.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application claims priority to U.S. Provisional Application No. 61 / 940,800, filed Feb. 17, 2014, the disclosure of which is incorporated herein in its entirety.FIELD OF THE INVENTION[0002]This invention is in the field of methods for the purification of naturally occurring materials having clinical importance, particularly the removal of endoxtoxins.BACKGROUND OF THE INVENTION[0003]Medical devices, such as dermal fillers or implants made from naturally occurring materials including polysaccharides, are in direct contact with organ tissue and therefore must be made from biocompatible materials. Such materials have to (1) be inert, (2) induce little or no immune response, and (3) in some cases be degradable by the organism. Unfortunately, medical devices can be contaminated during their manufacturing, transportation and / or storage. Contamination such as by microorganisms (e.g., bacteria, virus or spores) or chemicals can induce inflamma...

AI Technical Summary

Benefits of technology

The patent describes a method for removing endotoxin from various materials, such as polysaccharides. This method involves using acidic and basic solutions to break the bond between the lipid and polysaccharide molecules in endotoxins. This makes the fatty acid easier to remove with an organic solvent like ethanol. The polysaccharide component can also be altered by the hydrolysis process. This patent intends to provide a safe and effective way to remove endotoxin from various materials.

Problems solved by technology

Unfortunately, medical devices can be contaminated during their manufacturing, transportation and / or storage.

Contamination such as by microorganisms (e.g., bacteria, virus or spores) or chemicals can induce inflammatory responses, which can lead to fever, hypotension, systemic shock and even death.

Moreover, many of these materials are isolated from naturally occurring sources, such as microorganisms, and typically contain unacceptable levels of endotoxins.

One of the most serious contaminations that can occur in medical devices prepared from naturally occurring materials, such as polysaccharides, is endotoxins.

Due to their amphiphilicity, endotoxins are difficult to remove from commercially useful materials.

Autoclaving, which is a common technique used for sterilization, cannot remove endotoxins.

Moreover, the removal of endotoxins from commercially useful materials, such as agarose or carrageenan, is challenging since these materials themselves are polysaccharides.

Moreover, these techniques can also generate degradation products of the material, which can be toxic, or causes changes to its mechanical properties, affecting the proper operation of the device.

Unfortunately they cannot be used for the sterilization of polysaccharide, such as agarose, as they modify the polysaccharide backbone.

Dialysis, however, is an expensive and time consuming process.

Images